Sample processing module array handling system and methods

ABSTRACT

A handling system for high throughput processing of a large volume of biological samples is provided herein. Such systems can include an array support assembly that supports multiple diagnostic assay modules in an array having at least two dimensions, a loader that loads multiple diagnostic assay cartridges within the multiple diagnostic assay modules. The array support assembly can be movable relative the loader to facilitate loading and unloading so as to provide more efficient processing.

CROSS-REFERENCES TO RELATED APPLICATIONS

This Non-Provisional application claims the benefit of priority to U.S.Provisional Application No. 62/424,313 filed Nov. 18, 2016, the entirecontents of which are incorporated herein by reference.

This application is generally related to U.S. patent application Ser.No. 15/217,920 entitled “Molecular Diagnostic Assay System,” filed Jul.22, 2016 which is incorporated herein by reference in its entirety forall purposes.

BACKGROUND OF THE INVENTION

The present invention relates to the field of fluidic devices forcarrying out multiplex chemical or biochemical reactions and forperforming multiplex chemical and/or biochemical assays. Moreparticularly, this invention relates to a handling system for devicesconfigured for carrying out multiplex chemical and/or biochemicalreactions, and detecting a plurality of chemical and/or biochemicalcompounds.

Modern disease diagnosis, pathogen detection, gene discovery, drugdevelopment, and various genetic-related technologies and researchincreasingly rely on processing a large number of biological samples.Traditional methods of processing the samples one at a time have becomeincreasingly inadequate and the demand for performing assays on a largevolume of samples simultaneously has steadily increased, particularly inrecent years. Hence, there is a need for chemical/biochemical reactionsystems and devices that perform high-throughput assays.

Conventional high throughput methods can include the use of microarrays,such as a DNA microarray, which is typically a two-dimensional array ofDNA molecules attached to a solid substrate on its surface. A DNAmicroarray can provide a useful platform as a multiplexing detectiondevice. For example, each element of the array has a unique DNA sequencethat is used to recognize or detect a unique complementary DNA sequencein a prepared fluid sample. These DNA microarrays have fundamentallychanged conventional approaches of observing one or a few genes ormolecules at a time to observing pathways, networks, and a largecollection of genes and pools of molecules. Such DNA microarray chipsavailable today typically operate based on the hybridization of targetDNA or RNA molecules from the fluid sample in a solution phase withprobe DNA (e.g. oligonucleotides or cDNA) molecules immobilized on solidsubstrates of the array. The arrays do not however provide for a rapidcost-effective way of detecting low abundance targets that can indicatethe presence of an infectious disease or other pathogenic state, whichis more typically detected using sensitive methods such as real-timePCR. A real-time PCR system detects PCR products as they accumulateduring a PCR process and allows for improved speed and efficiency inperforming assay, but these systems are typically hindered by the needto process the samples as a “batch” thus resulting in a delay ofprocessing some samples until enough have been collected to make theoverall process more cost effective, but this leads to increasedturn-around-time. Such delays and increased cost lead to less efficiencyand overall increase in health care costs.

Sample preparation is another typical problem that hinders the speed atwhich large volumes of diagnostic assays can be performed. Although manysuch systems require separate processing of the fluid sample beforeintroduction into a real-time PCR diagnostic assay device, there areadvances in recent years that provide automated sample preparation thatis coordinated with real-time PCR analysis within a single analyticaldevice or system. One such device is the GeneXpert device developed byCepheid as described in, e.g., U.S. Pat. Nos. 8,048,386; 6,374,684, andU.S. patent application Ser. Nos. 13/843,739 and 15/217,920, eachincorporated herein by reference.

The current Cepheid systems are provided to an end-user as individualmodules, or a small system of grouped modules, or large scale systems.Currently available small systems provide an enclosure that includes asmall number of modules, e.g. 2, 4, 8 or 16 modules, while the largescale systems can provide 48 or 80 modules. The small systems are wellsuited for small-scale operations, but cannot provide the highthroughput demands of a large-scale operation, such as a laboratory ortesting facility.

Although commercially available large systems, including Cepheid'sInfinity 48 and 80 systems, provide a higher throughput of diagnosticassay testing, such systems are exceedingly large and typically requirelarge rooms that are accessible through oversized doors that allow fordelivery of such systems. These types of rooms are typically found in aclean setting of a hospital or laboratory and often must be speciallybuilt or modified to allow the system to be delivered and installed.This can require tremendous capital costs, in addition to theconsiderably high costs of the system, which can put installation ofhigh throughput analytical systems beyond the reach of some diagnostictesting centers and laboratories. Such systems are also exceedinglylarge and since floor space in such facilities can be difficult andcostly to obtain without displacing existing equipment or personnel,some facilities rely on undersized systems or multiple smaller systems,which often cannot meet the high throughput demands of the facility.These issues can result in a backlog or excessive wait times foranalytical results. For example, such facilities may take one to threedays (or more) to report a requested diagnostic test to the patient orphysician from when the sample is first collected, even though theassociated diagnostic assay may take only a few hours. Similar delayproblems are faced by systems that use “batch” processing. Such delaysare troubling, particularly when attempting to diagnose life threateningillnesses or screening individuals exposed to an outbreak of a pathogenor disease where unnecessary delays or isolation can cost lives andincreases overall healthcare costs.

Thus, there is a need for a high throughput handling system that allowsfor processing of a large volume of samples in a more efficient andexpedient manner. There is further need for such high throughputhandling systems that are amenable to being incorporated into existingtesting facilities where access, space and costs are of particularconcern.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to high throughput handling systems,devices and methods for processing of large volumes of biologicalsamples, and in particular systems for performing diagnostic assays asdetailed in the various embodiments as described herein.

In some embodiments, the invention provides a handling system for highthroughput processing of a plurality of biological samples, each samplebeing within a respective cartridge of a plurality of diagnostic assaycartridges. The system can include an array support assembly adapted tosupport a plurality of diagnostic assay modules in an array having atleast two dimensions, typically a cylindrical array. In someembodiments, the array has a shape other than cylindrical, for example,the array can be elliptical, hexagonal, octagonal, or other geometricalconfigurations suitable for use with the invention. Each diagnosticassay module includes a diagnostic assay system adapted for receiving adiagnostic assay cartridge and performing a diagnostic assay on abiological sample within the cartridge. The system can further include aloader adapted to load each of the plurality of diagnostic assaycartridges within a diagnostic assay module within the array. The arraysupport assembly is movable relative the loader such that the cartridgeis loadable in any of the modules within the array by moving the loaderrelative the array. In some embodiments, the array is a cylindricalarray that rotates along its longitudinal axis and the loader mechanismtranslates vertically in an elevator adjacent the cylindrical array.

In some embodiments, the invention provides methods of handling aplurality of biological samples with a high throughput processingsystem. Such methods can include: receiving multiple diagnostic assaycartridges in a high throughput processing system; and loading, with aloader, each of the plurality of diagnostic assay cartridges into arespective diagnostic assay module of a plurality of diagnostic assaymodules within an array support defining an array having at least twodimensions. Each module includes a diagnostic assay system adapted forreceiving a diagnostic assay cartridge of the plurality and performing adiagnostic assay on a biological sample within the respective cartridge.Loading can include moving the array support relative the loader suchthat the diagnostic assay cartridge is loadable in any of the diagnosticassay modules within the array by moving the array in combination withthe loader. In some embodiments, the array is a cylindrical arrayenclosed by an outer shell and the methods can further include cooling amicroenvironment of the array by forcing air upwards through an opencentral column and directing the cooling air through each row of thearray with one or more baffles between rows of the array within theouter shell.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A provides an overview of a high throughput handling system forperforming processing and diagnostic assays of a high-volume stream ofsamples, in accordance with some embodiments of the invention.

FIG. 1B shows a schematic illustrating the diagnostic assay module anddiagnostic assay cartridge(s) within the high throughput handling systemof FIG. 1A, in accordance with some embodiments.

FIG. 1C shows an exploded view of the high throughput handling system ofFIG. 1A, in accordance with some embodiments.

FIG. 1D shows a diagnostic assay modules assembly insertable into acircular level of the array of the high throughput handling system ofFIG. 1A, in accordance with some embodiments.

FIG. 1E shows a support assembly and rotation actuators to facilitaterotation of a circular level of the array of the high throughputhandling system of FIG. 1A, in accordance with some embodiments.

FIG. 1F shows an exploded view of the support assembly of FIG. 1E, inaccordance with some embodiments.

FIG. 1G shows an exploded view of an elevator assembly of the highthroughput handling system of FIG. 1A, in accordance with someembodiments.

FIG. 1H shows an exploded view of a base and loading tracking of thehigh throughput handling system of FIG. 1A, in accordance with someembodiments.

FIGS. 2A-2B depict a lab technician placing diagnostic assay cartridgesin queue for processing within a high throughput handling system havingan array of diagnostic assay modules, in accordance with someembodiments.

FIG. 2C shows a pair of diagnostic assay cartridges held within agrasper being lifted in an elevator of the system to facilitateplacement of one of the cartridges within a diagnostic assay module ofthe array, in accordance with some embodiments.

FIG. 2D shows a pair of diagnostic assay cartridges held within agrasper being lowered in the elevator to discard a spent cartridge, inaccordance with some embodiments.

FIG. 2E depicts a technician placing a diagnostic assay cartridge inqueue in the loading track and removing a waste receptacle from a baseof the system filled with spent cartridges, in accordance with someembodiments.

FIG. 3A-3C depict top and side views illustrating the relativedimensions of the array assembly and base that allows for transport ofthe array assembly with countertop removed through a standard sizeddoorway, in accordance with some embodiments.

FIG. 3D shows an overhead view of the array assembly with the counterremoved, in accordance with some embodiments.

FIGS. 3E and 3F show an overhead and side view, respectively, of a highthroughput handling system with a cartridge preparer that prepares andautomatically loads prepared diagnostic assay cartridges onto theloading track, in accordance with some embodiments.

FIG. 4 illustrates a high throughput handling system with an adjustableheight transport cart supporting the removable array assembly from thebase of the system, in accordance with some embodiments.

FIGS. 5-6 illustrate detail view of the elevator and loader for graspinga pair of diagnostic assay cartridges to facilitate loading and/orunloading from the diagnostic assay modules of the array, in accordancewith some embodiments.

FIG. 7 illustrates a specialized waste receptacle adapted for use with ahigh throughput handling system to collect spent cartridges thatincludes an optional lid and diverter, in accordance with someembodiments.

FIG. 8A illustrates a cross-sectional view of the high throughputhandling system to illustrate an integrated cooling system to controlheat transfer through the array of diagnostic assay modules duringoperation, in accordance with some embodiments.

FIG. 8B illustrates a cross-sectional view of the high throughputhandling system with a cooling system with intake fans integrated withinthe base, in accordance with some embodiments.

FIG. 8C shows a high throughput handling system with an external aircooler connected to the air intake of the base, in accordance with someembodiments.

FIG. 9 illustrates a cross-sectional view of the high throughputhandling system to illustrate the modular construction of each level ofthe array, in accordance with some embodiments.

FIG. 10 illustrates an ultra-high throughput handling system withdiagnostic assay module array, in accordance with some embodiments.

FIGS. 11-12 illustrates methods of performing sample processing using ahigh throughput handling system, in accordance with some embodiments.

FIG. 13 shows a comparison of throughput times for systems in accordancewith embodiments of the invention as compared to commercially availablesystems

FIGS. 14A-14D show alternative embodiments of module arrays and loadingtracks utilized in high throughput handling systems, in accordance withsome embodiments.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates generally to systems, devices and methodsfor providing high throughput performance in the analysis/testing ofbiological samples, as detailed in the various embodiments describedherein. The system utilizes an array of diagnostic assay modules thatare movable relative a loader to allow concurrent processing of a largevolume of biological fluid samples received in diagnostic assaycartridges within the array of modules. In some embodiments, thediagnostic assay modules are each capable of performing samplepreparation as well as a diagnostic assay of a fluid sample within adiagnostic assay cartridge disposed therein. Typically, the diagnosticassay modules can be independently operable such that the processing ineach module is performed separately from each other. Although in someembodiments the modules are identical, it is appreciated that the arraycan include differing types of modules as well. Such a configuration isadvantageous as individual modules can be removed/replaced and servicedas needed without adversely affecting or require dismantling of othermodules or mechanisms.

These and other aspects can be further understood by reference to thevarious embodiments shown in the following figures and described in thetext.

FIG. 1A depicts a high throughput handing system 100 having an arraysupport assembly 130 that supports an array of diagnostic assay modules30. In this embodiment, each module is configured with the same functionand capabilities for processing a fluid sample within a diagnostic assaycartridge 10 inserted and received therein. In this embodiment, thearray is a cylindrical array having four circular rows, each rowsupporting 25 diagnostic assay modules 30 such that the entire system100 includes 100 independent modules. Various other configurations,having more or fewer rows, or more or fewer modules per row could beutilized. System 100 includes two elevators 120 to facilitate loadingand unloading of the cartridges 10 from the modules 30 of the array.Each elevator includes a loader 20 adapted to releasably hold adiagnostic assay cartridge and position the cartridge into any of theavailable modules 30 and/or to remove a spent cartridge 10 from any ofthe modules 30 after processing to be discarded. Although thisembodiment includes two such elevators, more or fewer elevators could beutilized. Advantageously, the entire array of 100 cartridges can beloaded in about 10 minutes by a single elevator and can be loaded inless than seven minutes by use of two elevators. The above describedconfiguration allows for throughput and processing speeds that arevastly improved as compared to conventional processing systems. Eachcylindrical row is rotatable along a longitudinal axis of the array andthe elevator travels between rows of the array, typically by translatingvertically. In some embodiments, each cylindrical row rotates in stepssuch that a diagnostic assay cartridge receptacle bay of each diagnosticassay module is positioned adjacent the elevator for a time sufficientto facilitate loading and/or unloading of a cartridge, at least a secondor more, typically a few seconds (e.g., 3-5 seconds), in someembodiments, about 10 seconds or more. Such a configuration allows forready access to any of the modules by combined movement of the elevatorand the array, such that the diagnostic assay cartridges can be loadedand unloaded from modules 30 considerably faster than a system having aplanar rectangular array of receptacles for receiving such cartridges.In some embodiments, the rows of the array revolve separately from eachother, for example, adjacent rows can travel in opposite directions, andin some embodiments, each row can travel in the same direction or theentire cylindrical array can be fixed and revolve as a single unit. Insome embodiments, not all rows of the array rotate. For example, one rowof the array can be held stationary, while the remaining rows of thearray rotate (either together or in opposite directions).

In some embodiments, the modules of the array are independently operableand are electrically and communicatively coupled with a central powersource and communication platform, which can be housed within a base 160of the system. Base 160 includes two doors that house one or more wastereceptacles into which spent diagnostic assay cartridges areautomatically discharged after processing. A waste capacity indicator162 (e.g. LED) indicates to a user that the receptacle is full. Theindicator 162 can be lit in response to a determination that thereceptacle is full, based on a diagnostic assay cartridge count or aweight of the receptacle. In some embodiments, the waste capacityindicator 162 can indicate differing states as the waste receptaclefills, for example, green/yellow/red corresponding to partly empty/nearfull/completely filled. In some embodiments, the indicator 162 isdisposed on a central post on an interior of the base and the handles ofthe doors are translucent to allow a user to view the indicator LEDthrough the handles. Base 160 can also include proximity sensor 163 thatdetects approach of personnel and initiates rotation of the loadingtrack to receive cartridges to be loaded for analysis. Base 160 canfurther house various control, power and communication features or hubsto facilitate coordinated control of system components and automation ofthe system. As shown in FIG. 1H, base can include controller 180,automation computer 181, power distributor 182 and communication hub 183(e.g. ethernet hub). It is appreciated that the controller, automationcomputer and communication hub can include hardwired communicationand/or wireless communication. Further, such features can be centralizedor divided among multiple units. For example, controller 180 caninitiate various control aspects of the overall system and communicatewith individual controllers associated with each of the modules of thearray.

In some embodiments, each diagnostic assay module 30 is configured toreceive a diagnostic assay cartridge having a reaction vessel or tubeextending from the cartridge configured for detection of a nucleic acidtarget in a nucleic acid amplification test (NAAT), e.g., PolymeraseChain Reaction (PCR) assay. Preparation of a biological fluid sample insuch a cartridge generally involves a series of processing steps, whichcan include chemical, electrical, mechanical, thermal, optical oracoustical processing steps according to a specific protocol. Such stepscan be used to perform various sample preparation functions, such ascell capture, cell lysis, purification, binding of analyte, and/orbinding of unwanted material. In some embodiments, the diagnostic assaycartridge can include one or more chambers suited to perform the samplepreparation steps. A diagnostic assay cartridge suitable for use withthe invention is shown and described in U.S. Pat. No. 6,374,684,entitled “Fluid Control and Processing System” filed Aug. 25, 2000, andU.S. Pat. No. 8,048,386, entitled “Fluid Processing and Control,” filedFeb. 25, 2002, the entire contents of which are incorporated herein byreference in their entirety for all purposes. The arrays of modulesdescribed herein can include modules in accordance with those detailedin U.S. patent application Ser. No. 15/217,920 entitled “MolecularDiagnostic Assay System,” filed Jul. 22, 2016. It is appreciated,however, that the systems described herein can include various othertypes of modules and cartridges as well, as will be known to persons ofskill in the art.

Non-limiting exemplary nucleic acid amplification methods suitable foruse with the invention include, polymerase chain reaction (PCR),reverse-transcriptase PCR (RT-PCR), Ligase chain reaction (LCR),transcription mediated amplification (TMA), and Nucleic Acid SequenceBased Amplification (NASBA), and isothermal amplification. Additionalnucleic acid tests suitable for use with the instant invention are wellknown to persons of skill in the art. Analysis of a fluid samplegenerally involves a series of steps, which can include any of: opticaldetection, electrical detection or chemical detection, according to aparticular protocol.

FIG. 1B shows such a diagnostic assay cartridge 10 adapted for use witha diagnostic assay module 30 within the array of modules supported bythe array support assembly 130. When using the module 30 separately fromthe array in system 100, a user inserts the cartridge 10 directly into areceiving bay behind door 31. The module 30 can be configured to opendoor 31 when the bay is empty and the module 30 is ready to performsample processing or when sample processing is complete to facilitateremoval of the spent cartridge. In system 100, the diagnostic assaycartridges are placed in a queue within a loading track 110, whichrevolves around the cylindrical array to transport each cartridge 10 tothe elevator 120. The loader 20 then picks up each cartridge to beprocessed and the loader translates vertically along the elevator to theappropriate row of the module in which the cartridge is loaded. Thebasic elements of system 100 can be seen in the exploded view shown inFIG. 1C, which shows the four levels of the array support assembly 130,each level having multiple diagnostic modules 30 mounted therein, thetransparent shell 135 that encases the array to allow a cleantemperature controlled environment to be maintained, two elevators 120,counter 114 and base 160 with cartridge loading track 110. Elevators 120can be further understood by referring to the exploded view shown inFIG. 1E. In some embodiments, loading track 110 is cylindrical, but itis appreciated that loading track 110 can be any geometrical shape aslong as the track connects back on itself such that the track iscontinuous and recirculates.

FIG. 1D shows an individual rotatable level of the array support 130that supports multiple diagnostic assay modules 30 therein. Eachdiagnostic assay module 30 is contained within a carrier 141 having acarrier cover 142 with a front opening to allow access to the loadingbay of a respective module 30. The carrier 141 is securely attached tocorresponding supports within the array support 130, which can befurther understood by referring to FIG. 1E and the exploded view of thearray support shown in FIG. 1F. The support includes a slip ring, whichincludes a fixed slip ring portion 131 at its center, which carriespower and data through a rotating union, and a rotating hub 137 whichinterfaces with an upper frame 136 that includes engineered cutouts forinterfacing with and securely attaching multiple module carriers 141therein to support the modules within the level. A circuit board 139(e.g. PCB) disposed near the bottom electrically interface with each ofthe modules when mounted therein. Upper frame 136 is coupled with a ringgear 132, which is rotatably controlled by motor 134 via drive mechanism133 to allow each level to be incrementally rotated, as describedherein. Motor 134 can be a server motor, stepper motor or any suitablemotor. Drive mechanism 133 can be a drive belt, cable, screw, gear orany suitable drive mechanism. Movement of the level of the array can becontrolled by controller 138. In some embodiments, controller 138 caninclude power control and motor motion control. Associated componentscan include a power transformer, power production distributor andvarious power distribution components. Baffle 52 interfaces with thebottom of the support and facilitates controlled airflow through eachlevel. In some embodiments, the baffle along the bottom of each leveldiffers between each level to provide graduated destratification ofairflow between levels, providing more airflow where needed.

System 100 can include a controller that coordinates movements betweenthe various components of the system described herein. For example, eachmodule 30 can communicate, either directly or wirelessly, to the centralcontroller such that the controller can identify which modules 30 areempty and can direct the elevator to the appropriate row to arrive atthe identified module 30. In some embodiments, each module communicateswith a diagnostic assay cartridge 10 inserted therein by near fieldcommunication (NFC) by which an ID of the cartridge containing abiological fluid sample and an appropriate assay protocol is obtained bythe module 30. Likewise, the module 30 communicates when a sampleprocessing is completed and the cartridge is ready to be removed suchthat the controller sends a command to the loader to translate along theelevator to the appropriate location to remove the spent cartridge.Although the elevator moves on command to a particular verticallocation, the rows of the array support moves in regular increments(typically, a rotation sufficient to move the next adjacent column ofdiagnostic module of the array to the elevator) at regular intervals(typically, at least one second or more to allow loading/unloading of adiagnostic assay cartridge into a module or removal of spent cartridgesfrom a module). In some embodiments, the array support is controlled torotate in larger increments that skip one or more adjacent columns,which may promote more even distribution of loaded modules. Theload/unload times for cartridges is short, given the large number ofmodules (typically 4 rows×25 modules/row), a module having an empty bayfor loading or a module having a spent cartridge for unloading willarrive at one of the elevators in short order. Indeed, the entire arrayof 100 modules can be loaded in approximately 10 minutes.

In some embodiments, the diagnostic assay modules have a communicationssubsystem that can include a diagnostic component. A processor can becommunicatively coupled with the communications subsystem and thediagnostic component. The processor can be configured to cause thediagnostic assay module to wirelessly receive, using the communicationssubsystem, a command from a mobile device. The processor can also beconfigured to wirelessly send, using the communications subsystem, amodule command response to the mobile device. The processor can also beconfigured to conduct a test using the diagnostic module. The processorcan also be configured to wirelessly send, using the communicationssubsystem, encrypted diagnostic information (e.g., medical information),indicative of a result of the test, to a remote server.

FIGS. 2A-2E illustrates the process of a technician loading diagnosticassay cartridges 10 in a high throughput handling system 100 forprocessing within diagnostic assay modules 30 of the array and removingspent cartridges from the system 100.

In FIG. 2A, the technician places individual cartridges 10 to beprocessed within recesses of the loading track 110 of system 100 whilethe loading track incrementally rotates toward elevator 120. Loader 20is lowered along vertical elevator 120 and grasps a cartridge 10 a to betested. In some embodiments, the elevator includes a sensor that senseswhen a cartridge is ready to be picked up such that a central controllercan direct the loader 20 to grasp and hold the cartridge 10 a from theloading track 110. If any of the modules 30 within any of array rows 130a, 130 b, 130 c, 130 d, are empty, the controller commands the loader 20to translate along the elevator to any row having an empty module 30.Loader 20 then loads the diagnostic assay cartridge 10 a into therespective module. In this embodiment, the loader is configured to flipor rotate such that the loader can hold a pair of cartridgessimultaneously. Such a configuration further improves speed andefficiency since after loading of cartridge 10 a, the loader can flip toload the other cartridge, or could be used to remove a spent cartridge10 b before loading of cartridge 10 a. To discard spent cartridge 10 b,loader 20 lowers and releases spent cartridge 10 b above waste chute 116to be collected in a waste receptacle stored in base 160. If there areno spent cartridges to remove, the dual sided loader 20 could be used topick up two cartridges 10 a to be loaded for sequential loading intoempty modules 30 and/or the dual sided loader could be used to pick uptwo spent cartridges from two modules 30 for disposal.

In some embodiments, the controller commands the loader to translate tothe nearest empty module, although in other embodiments, the controllercommands the loader to translate to a module to distribute thecartridges more uniformly within the respective modules of the array. Insome embodiments, the controller commands the loader to only pick upcartridges for a particular assay. In some embodiments, assays of aparticular type are all loaded onto a particular row of the array. Insome embodiments, the controller commands the loader according to anumber of factors, which may be combined or weighted according tovarious differing objectives or combinations of objectives. Suchobjectives include, but are not limited to: proximity, temperature, loadbalance, heat balance, distribution among levels or within a respectivelevel, time length of assay, or any combination thereof. In someembodiments, the system can determine a preferred module, a preferredlevel of a particular array, or a preferred array for loading of acartridge based on one or more objectives or factors, including but notlimited to any of those described herein.

FIG. 2B shows another view of the technician loading diagnostic assaycartridges 10 a to be processed onto the loading track 110. In addition,a pair of emergency stop buttons 114 e are disposed on the countertop114. It is appreciated that one or more emergency stop features could beincluded on various other portions of the system in the alternative orin addition. As can be seen, loading track 110 can include recesses 111adapted to receive the cartridges. In any of the embodiments herein, theloading track can be continuous and/or recirculating. Loading track canbe defined as multiple components that fit into a rotating ring 112 ofmain casting 113, which can be seen in the exploded view of base shownin FIG. 1H. Some embodiments could utilize any type of recirculatingtrack configured to receive multiple cartridges. Such tracks couldinclude a non-linear track, as shown, or a linear track having arecirculating surface (e.g. conveyor belt). Such tracks can include acartridge receiving surface, which could include any of a recess, aprotrusion, a coupling feature, a hook, magnet, or any feature suited toreceive a cartridge and optionally maintain the cartridge in aparticular orientation. Alternatively, the track could receive themultiple cartridges in any orientation, and the orientations aresubsequently adjusted by an adjustment feature (e.g. gripper, orientingfeatures, interfacing surfaces, or any suitable mechanism). In someembodiments, the loading track could include independently movablecarts, each configured to support one or more cartridges. In someembodiments, the system includes at least one emergency stop buttonlocated on the counter, which shuts off power to the loading track andthe elevators. In the embodiment shown in FIG. 1H, loading trackincludes recesses 111, each recess dimensioned to receive a respectivecartridge. Recesses 111 are specially contoured so as to receive thecartridges in a proper location and orientation to facilitate graspingof the diagnostic assay cartridge by loader 20. In some embodiments,this can be accomplished by use of interfacing features (e.g.hole/pegs), or protrusion or ridges that constrain the cartridges in theproper location and orientation. In some embodiments, the track is acontinuous molded structure. In some embodiments, the holders for thecartridges are not connected and are individually separated, where eachholder contains only a single cartridge. In some embodiments, theholders are arranged in small groups to hold a subset of cartridges(e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10 or more cartridges). In someembodiments, the cartridge holders can be removed from the track forfilling with cartridges away from the system and the filled rack canthen be placed on the track for loading onto the array. In someembodiments, the system is configured to select certain cartridges fromthe recirculating track for loading into the array while allowing othercartridges to recirculate for one or more passes by the loader forsubsequent loading into the array. Such selection can be determinedbased on data obtained from the cartridge so as to prioritize loadingbased on one or more factors, including but not limited to, any of: rushstatus, sample ID, type of sample, type of assay, and an assay length.

FIG. 2C shows another view of the loader 20 grasping cartridges 10 a, 10b. As can be seen, the loader 20 can be translated along elevator 120 toany row of the array 130 and can discard cartridge 10 b by lowering andreleasing the cartridge into waste chute 116, as shown in FIG. 2D. FIG.2E shows a technician loading cartridges 10 into the loading track 110and in the process of removing waste receptacle 60 by opening base doors161, the waste receptacle 60 having been positioned beneath waste chute116 within the base 160 to collect spent cartridges. Receptacle 60 canbe easily removed for cleaning. In some embodiments, the base 160includes a waste receptacle excluder 164 designed to prevent insertionof the waste receptacle 60 if the correct flap is not opened and snappedinto place.

One particularly advantageous aspect of the above-described cylindricalarray configuration is that the array support assembly 130 can bedefined to have dimensions suitable for transporting the array through astandard sized doorway. This allows system 100 to be set up in virtuallyany suitable location and does not require an oversized entry, as domany conventional large-scale analysis systems. In addition, thecylindrical array configuration allows for a substantially reducedfootprint, which allows the system to be used in a variety of locationssince it does not require an inordinate amount of floor space, as domany conventional systems. In some embodiments, the system 100 (withoutthe counter) has a width of about 34″ or less and a height of about 74″or less. These dimensions substantially maximize the capacity of thearray assembly while still allowing the system to be easily transportedthrough a standard doorway, typically 80″ high by 36″ wide, even whenlifted off the floor by 1-2″ such as by a wheeled transport cart. Thedimensions of base 160 are well within suitable limits for transportthrough a standard doorway. The circular counter 114 that sits betweenbase 160 and array 130 can be removed and transported vertically ifneeded, for example, to reduce the overall width to allow passagethrough a standard doorway. In some embodiments, the internal crate andpackaging used to support the instrument during shipping can be used asa transport cart to move the instrument to its final destination in thelaboratory or hospital setting. In some embodiments, the internal crateand packaging that is also used as a transport cart is constructed ofwood. Exemplary size dimensions can be further understood by referringto FIGS. 3A-3D below.

FIG. 3A-3C depict top and side views illustrating the relativedimensions of the array assembly. As seen in FIG. 3A, the system 100with the counter attached has a minimum width, w. In this exemplaryembodiment, w is about 45.5″. As can be seen in FIG. 3B, the maximumwidth, W, occurs along the counter 114. In this embodiment, W is about51″. As can be seen in FIG. 3C, the system 100 has an overall height, h.In this embodiment, h is about 74″. As described previously, the countercan be removed to facilitate shipping and transport of system 100through a standard sized doorway. As can be seen in FIG. 3D, in thisembodiment, the system 100 with the counter removed has a reduced width,w′. In this embodiment, w′ is about 34″ which allows the system 100 toeasily fit through a standard sized doorway. Although advantages ofcertain dimensions have been described herein, it is appreciated thatother embodiments could include a similar system or components withvarious other dimensions in accordance with any of the conceptsdescribed herein. Advantageously, the counter 114 and loading track aresuch that the system can be accessed from all sides (e.g. 360 degrees)such that cartridges can be loaded by one or more personnel approachingfrom multiple directions. It is appreciated that in other embodiments,the counter 114 and loading track can be configured such that access isfrom less than 360 degrees (e.g. 270 degrees, 180 degrees, or less). Asshown, in FIGS. 3A and 3D, the countertop 114 and system 100 can beconfigured with a generally circular shape with one flattened side. Thisallows the system to be placed against a wall if needed. It isappreciated that the system and countertop, however, could be configuredin any shape with or without a flattened side, including circular,polygonal (e.g. square, hexagonal, etc.) or any regular or irregularshape desired.

In some embodiments, the system can further include an automatedcartridge preparer, which can be configured to perform one or morepre-analytic steps that can include such processes as adding thebiological sample to be tested to the cartridge, closing the cartridgelid and preparing the cartridge for loading onto the array. By use of acartridge preparer, wear and tear on the modules affixed within thearray can be further reduced, as can technician time which is typicallyused for pre-analytic cartridge processing. The cartridge preparer canbe further configured to position a diagnostic assay cartridge withinthe loading track of the system after performing the pre-analyticprocessing. FIG. 3E shows an exemplary embodiment in which system 100includes cartridge preparer 115 positioned adjacent the loading track110. As can be seen in FIG. 3F, cartridge preparer 115 can include acartridge loader for positioning a prepared cartridge 10 within loadingtrack 110. It is understood that the sample loader of the cartridgepreparer 115 can include similar mechanisms as those described in thearray elevators, or any suitable mechanisms as would be known to one ofskill in the art.

In some embodiments, system 100 can include a transport cart 170 tofacilitate transport and assembly of system 100 at a desired location.As shown in FIG. 4, the transport cart 170 can include a lifter 171controlled by crank 172, multiple cranks or other such user controlmechanisms, which may include hydraulic, electrical, pneumatic, controlor lift mechanisms to allow the system 100 to be lifted off the groundand wheeled into a room. The transport cart 170 provides a more stablemanner in which to move the system 100, which may be preferable giventhe small footprint and relative height of the system. This approach isadvantageous as it allows the array assembly 130 to be delivered andtransported to its destination as a substantially assembled unit despiteits considerable weight and dimensions. The removable counter can thenbe mounted to the system once it is delivered to its final destination.Typically, the base and array assembly are securely and fixedly attachedone another. In some embodiments, the array assembly can be removed fromthe base to facilitate shipping or transport and can be assembledon-site. In some embodiments, the base can include wheels to allow thesystem to be moved or transported without any transport cart.

FIGS. 5-6 depict detailed views of the cartridge loader 20 in elevator120. As shown in FIG. 5, elevator 120 includes a track 121 which guidesvertical movement of a vertical carriage 122, which is powered andcontrolled by the central controller in response to sensors and/ordetermination of empty modules 30 or spent cartridges based oncommunication with the modules 30. In this embodiment, loader 20includes two graspers 22, each having a pair of contoured jaws that arespaced apart to grasp the outer edges along the front face under theautomation flange of each cartridge 10, as shown. The two graspers 22extend from a central member or shaft 21 that is rotationally orpivotally coupled to a horizontal carriage 23 that translates along apair of rods 123 extending from vertical carriage 122 towards the array130. Movement of the horizontal carriage in combination with movement ofthe grasping jaws allows the loader to pick up each diagnostic assaycartridge to be loaded as well as place the cartridge 10 within areceptacle bay of a respective module 30. Movement of the horizontalcarriage 23 towards track 121 also allows loader 20 to align any spentcartridges above the waste chute 116 to be discarded, as shown in FIG.6. These components can be further understood by referring to theexploded view in FIG. 1G.

Elevator 120 can further include one or more sensors for detectingproximity of an approaching diagnostic assay cartridge in the loadingtrack and obtaining data from the cartridge before loading. For example,as shown in FIG. 6, a proximity sensor 125 disposed within the entryinto elevator 120 detects the approaching cartridge, which signals tothe elevator to pick up the cartridge. In addition, a data sensor (e.g.NFC sensor) detects an ID of the diagnostic assay cartridge and adiagnostic assay protocol for the cartridge, which in some embodiments,can be used to determine where the cartridge should be loaded onto thearray. In some embodiments, an NFC sensor is used to identify a givencartridge. In some embodiments, the sensor used to detect the diagnosticassay cartridge can employ optical recognition technology (bar codes, QRcodes), RFID tags, and infrared (IR) detection. Additional sensordetection methods will be well known to persons of skill in the art.

FIG. 7 depicts an exemplary waste receptacle 60 adapted for use with theabove-described system. Waste receptacle 60 is specially shaped to fitwithin base 160 so that a narrowed portion extends under waste chute116. In some embodiments waste receptacle 60 includes a main receptaclebody 61 that can be formed in various other shapes, e.g. square, round,oval, etc. Waste receptacle 60 is typically formed of a rigid polymerand can be formed so as to be suitable for reuse or to be disposable. Insome embodiments, waste receptacle 60 further includes a lid 63 thatincludes end flaps 63 a that are adapted to fold upward against mainportion 63 b. End flaps 63 a can further include coupling feature 64 athat interfaces with a corresponding coupling feature on 64 b so as tohold the respective end flap in the upwardly folded position, whichallows a sufficient opening for spent cartridges to be directed into thewaste receptacle while the lid remains on top of the waste receptacle60. In some embodiments, a waste receptacle can include an excluder thatprevents the waste receptacle from being inserted into base 160 if thecorrect flap is not opened. Such a lid is particularly useful since somediagnostic assays are performed on biological fluid samples that maycontain biohazardous material (e.g. infectious waste or hazardouschemicals) such that contact with the spent cartridges should avoided orminimized.

After the waste receptacle 60 is sufficiently filled, it can be removedfrom base 160 and the end flap 63 a can be folded downward and theentire lid secured and/or sealed against the outer edge opening of thewaste receptacle so that the contents can be discarded within the sealedreceptacle without having to empty the waste receptacle or transfer thecontents. In some embodiments, the waste receptacle can include adiverter 62, which can include angled portions 62 a, 62 b so as todirect any discarded cartridges into the waste receptacle. In someembodiments, the waste receptacle can include dividers or can use one ormore disposable bags such that the diverter can keep spent cartridgesdeposited through a first opening separate from spent cartridgesdeposited through a second opening on the opposite end. Diverter 62could further include a lip or ridge 62 c along one or more sides so asto inhibit prevent any leakage or residue from spent the cartridges.

In performing assays, it is desirable and often necessary to maintain anambient temperature within a suitable range to maintain hardwarefunctionality, assay integrity and improve testing efficiency. In someembodiments, the ambient operating temperature range for the modules isfrom about 10° C. to about 40° C. In performing sample processing anddiagnostic assays concurrently with a large number of modules (e.g. 100or more), a considerable amount of heat can be created. Further, manysuch diagnostic assays utilize thermal cycling to amplify the targetanalyte in the fluid sample, which can further contribute to the overallheat being generated. Since heat rises this can result in a substantialtemperature differential between the top-most row of the array 130 ascompared to the bottom-most row. Thus, to maintain a suitable ambienttemperature for each module of the array 130, system 100 can include anintegrated cooling system.

FIG. 8A illustrates a cross-section of system 100, which reveals thedesign of an internal cooling system 150 incorporated into the structureof the array assembly 130, which is detailed further in FIG. 9. Arrayassembly 130 is composed of four levels, each having a main circularframe, 130 a, 130 b, 130 c, 130 d. Each frame includes features forattaching and securing the module 30 to the respective frame. Each levelis further designed such that each level is isolated or baffled fromeach other level with regard to air flow. The frames can define an opencentral column through which the longitudinal vertical axis of the frameextends with openings adjacent to each of the modules 30 attached to theframe. Cooling system 150 utilizes this open central column and openingsadjacent the modules to force air through the array support assembly130. The array support assembly 130 is enclosed in an outer cylindrical,transparent outer shell 135, which protects the modules 30 from dirt anddebris and allows a microenvironment to be established and allows apositive pressure to be maintained around the array support assembly. Insome embodiments, each of elevators 120 can be encased in an outer shellthat merges with the outer cylindrical shell 135 such that the inside ofeach elevator is open to the interior of the cylindrical shell 135. Insome embodiments, the elevators are open to air flow on each level andact as “chimneys” for removing hot air from within the array assembly.

One or more cooling fans draw cool air in from the bottom of the arrayassembly through the open central column and outward through each of themodules 30 before the air travels upwards along the inside of outershell 135, and within the elevator columns, and outward through a top ofthe array assembly 135. In some embodiments, positive pressure ismaintained within the array assembly, as compared to an ambientenvironment. In some embodiments, the rate of air flow through the opencentral column is about 250 cubic feet per minute. The airflow path isshown by the dashed arrows in FIG. 8A. As can be seen in FIG. 8B, asingle fan 50 a is positioned beneath the open central column and one ormore auxiliary fans 50 b can be used to provide additional air flowthrough the lower level. In some embodiments, the first level 130 adoesn't receive any air from the open central column since the first airexit holes in the column are above the first baffle 52, thus auxiliaryfans 50 b can be used to direct air through the first level 130 a. Insome embodiments, the first exit air holes in the column are below thefirst baffle 52, thus allowing the first level 130 a to receive air fromthe open column (not shown). System 100 can include a cool air intake 50c that feeds column cooling fan 50 a and auxiliary fans 50 b with an airsupply at a controlled temperature (not shown). Cool air intake 50 c caninclude one or more fans, such as intake fans 50 d, 50 e and an airfilter 50 f. In some embodiments, for example systems having between 50and 200 modules, this configuration allows an optimal temperature rangeto be maintained in the microenvironment of the array so long as the airintake is about 70° F. or less. Thus, in a room with an ambienttemperature of about 70° F., an air intake open to the ambient room maybe sufficient to maintain a suitable temperature controlled environmentfor the array, assuming the room has sufficient temperature control(e.g., air conditioning) to maintain an air supply of a consistenttemperature. In other embodiments, such as that shown in FIG. 8C, anexternal cool air supply 50 g can be connected to cool air intake 50 c,so as to ensure a sufficiently cool air supply regardless of the ambienttemperature. Such a configuration may be particularly useful in hightemperature or uncontrolled environments.

Since heated air tends to accumulate in the uppermost portion of thearray assembly, cooling system 150 can further includes baffles 51, 52,53, 54, 55 between row levels, that are adapted to direct and controlair flow 56 through the assembly. Lower-most baffle 51 extends to theinside of the exterior shell so that the air flow is directed throughthe open central column and through the modules of the first row.Baffles 52, 53, 54 separate each of the four rows above the first levelso that cool air supplied through the open central is supplied directlyto each row via the open central column. In some embodiments, baffles52, 53, 54 are smaller and do not extend entirely to the outer shell 135so as to allow flow of heated air passed through lower rows to travelupwards along an inside of the outer shell 135 towards the top mostopening. Any of baffles 51-55 can include one or more holes tofacilitate passage of air flow through the baffle as needed. In someembodiments, the baffles can be configured for level stratification andair management between levels. Top-most baffle 55 blocks the opencentral column but allows air flow through the inside of the outer shellto direct air flow to exit the system from one or more opening along thetop of system 100. A top vent 151 can allow air to exit around the edgesand top vents 152 on elevators 120, which allows each elevator to act asa chimney drawing heated air from each of the levels of the array.

In some embodiments, the system includes a temperature controllerconfigured to maintain the environment of the array assembly withinrange of temperatures suitable for processing of the samples within themodules of the array. In some embodiments, the temperature controller isconfigured to maintain the temperature of the ambient environmentbetween about 10° C. to about 40° C. so as to be suitable for performingPCR with the diagnostic assay modules. Preferably, the temperaturecontroller maintains the temperature below 40° C. In some embodiments,the range of suitable temperatures is between about 65 and 95 degreesFahrenheit. In some embodiments, the temperature controller maintainsthe temperature within a pre-defined delta (e.g. 2 degrees) from atarget temperature. In some embodiments the temperature controllermaintains the temperature within 1° C. from a target temperature. Thisimproves efficiency of analysis as well as consistency andpredictability of analysis time. In some embodiments, the temperaturecontroller is configured to adjust a temperature of an external aircooler that supplies air to the air intake. In some embodiments, thetemperature controller is configured to adjust the air flow through thesystem by adjusting fan speed (e.g. speed up air flow/adjust air flowbetween levels), as needed in order to facilitate cooling, particularlyas the system is nearing capacity. In some embodiments, the airflowthrough the system can be adjusted between levels such that more air isdirected to the levels where temperature is exceeding optimal levels. Insome embodiments, the system further includes diverters that can directair from the open central column to each of the different rows of thearray. For example, the diverters can be configured such that each ofthe four rows of the array each receive about 25% of the air flow fromthe open central column. In some embodiments, the diverters can beconfigured such that all of the air flow in the open central column isdiverted to a particular row in the array. In some embodiments, each rowof the array can receive anywhere from substantially none (0%) of theair flow in the open central column to receiving substantially all(100%) of the air flow from the open central column or anywhere inbetween. In some embodiments, the percentage of air flow allocated to aparticular level increases with each level in an upwards direction. Thisallows the levels to be cooled in proportion to the amount of heat thataccumulates. For example, in an exemplary four level configuration, thelowest level can receive between 0-10%, the next higher level canreceive between 10-20%, the next higher level received between 20-50%and the highest level receives between 40-80% of the airflow. It isappreciated that various other allocations of airflow between levelscould be realized. The temperature controllers can be communicativelycoupled with one or more temperature sensors (e.g. thermocouples)disposed at one or more locations within the array to facilitateimproved temperature control.

FIG. 9 shows a cross-sectional view illustrating the four circularframes defining the array assembly. Each of the circular frames arerotatably coupled within the assembly and operably coupled with a driveror drive mechanism controlled by the controller such that each frame canbe rotatably driven so that each row of the array incrementally rotates.Typically, the structure is configured and controlled such that adjacentframes incrementally rotate in opposite directions (e.g. 130 a rotatesclockwise, 130 b rotates counterclockwise, 130 c rotates clockwise, 130d rotates counterclockwise or vice versa). It is appreciated, however,that various other configurations and movement schemes are within thescope of the invention. Power and communication is supplied to each ofthe modules 30 in each frame through power and communication cables thatextend through the central column and between each rotating framethrough slip rings, which allow passage of power and data through arotating union. In some embodiments, the slip rings include holes tofurther facilitate passage of air from the central column into each ofthe levels of the array assembly. Thus, the modules 30 of the array 130remain electrically and communicatively coupled to a common power sourceand communication unit of the central control during the differentialrotational movement of the array.

FIG. 10 illustrates an embodiment showing an ultra-high throughputhandling system 200, which includes two systems 100′ substantiallysimilar to those described herein, which are integrated into a singlesystem. The system can be defined by same or similar structures as thepreviously described embodiments with minor modification, such as amodified countertop 114 that extends between two columnar arrays. Insome embodiments, the two arrays share a single loading track that canbe in the shape of an oval circulating around both arrays. Such aconfiguration provides ever further improvements in speed and efficiencyfor processing extremely high-volume streams of diagnostic assaycartridges.

FIGS. 11 and 12 depict methods of loading and unloading diagnostic assaycartridges from a high throughput system in accordance with theinvention. FIG. 11 shows a method of automatically loading a diagnosticassay cartridge into an available diagnostic assay module in a circulararray of a high throughput handling system. FIG. 12 shows a methods ofunloading and discarding a spent diagnostic assay cartridge from adiagnostic assay module in a circular array after processing iscomplete.

As depicted in FIG. 11, such a method can include a step of sensing adiagnostic assay cartridge to be analyzed in a loading track of a highthroughput handling system having an array of diagnostic assay modules.Sensing can include detecting proximity of the cartridge and/or readinginformation from the cartridge (e.g. ID, assay type, etc.). Next, thesystem can facilitate loading of the cartridge into the array.Typically, loading includes grasping the cartridge with a loader andloading into an available module. The method can further includeidentifying a diagnostic assay module within the array that is empty andavailable to perform sample processing based on communication with themodule. Optionally, the method can include determining a preferreddiagnostic module in which to load the sample from multiple availablemodules. Determination of a preferred module can be based on any of:proximity, temperature, load balance, heat balance, distribution amonglevels or within a respective level, time length of assay, or anycombination thereof or any factor desired. The loader then moves thecartridge to the array until the loader is adjacent the identifiedmodule in the array and loads the cartridge into the empty bay of theidentified or preferred module.

As depicted in FIG. 12, such methods can include a step of receiving acommunication from a diagnostic assay module in an array of a highthroughput handling system that sample processing is complete. Next, themethod can entail identifying a location of the module within the array,then moving a loader/unloader relative the array until adjacent theidentified module. This can include waiting until the array is moved toan appropriate position so that the loader can intercept the identifyingmodule when the respective column is moved adjacent the loader. Next,the spent cartridge is removed from the module and moved away from theidentified module and released or discarded into a waste receptacle.

FIG. 13 illustrates throughput of samples on the 100 module system ofFIG. 1A (Omega 100) and the 200 module system of FIG. 10 (Omega 200) ascompared to conventional high throughput systems (Cepheid Infinity-80,Roche Cobas 4800, BD Viper XTR, Hologic Panther, and Abbott M2000).Throughput data for the Omega system was modeled based on simulationmodels of the Omega 100 and Omega 200 systems and utilizing availabledata from each of the commercial systems noted. The data for thecommercial systems was obtained from the study by Jang et al. (SexuallyTransmitted Disease (June 2016) Vol 43(6):377-381. This data is alsoprovided in Table 1 below. As can be seen, the time required to processa large number of samples with the Omega system is considerably lowerthan any of the other commercially available systems as shown, forexample analysis of 192 sample in the Omega 200 system can be performedin less than half the time required by other commerically availablesystems.

TABLE 1 Time Comparison of High Throughput Systems Omega Omega CobasViper Samples 200 100 Infinity 4800 XTR Panther M2000 1 1:30 1:30 1:313:15 3:42 4:05 4:35 10 1:34 1:34 1:40 3:16 4:06 4:11 5:04 24 1:40 1:402:03 3:36 4:08 4:32 5:21 48 1:50 1:50 2:13 3:49 4:13 5:01 5:48 96 2:102:10 3:54 5:03 5:13 5:55 7:15 192 2:50 4:04 6:45 7:47 7:25 7:43 12:07 

FIGS. 14A-14D illustrate alternative embodiments of a high throughputprocessing systems, in accordance with aspects of the invention. FIG.14A shows system 300, which includes a circular array of modules 301 andloading track 310. Similar to other embodiments, loading track 310 is arecirculating track that transports diagnostic assay cartridges to aloader, however, track 310 includes movable cartridge carriers 311(e.g., carriages or “boats”) that circulate within the track. In someembodiments, each cartridge support can be independently movable withinthe loading track and can be removed and replaced as needed. Eachcarrier 311 can include a support feature, such as a contoured recess orother suitable feature for releasably supporting the cartridge withinthe carrier. FIG. 14B shows system 400, which includes a hexagonal arrayof modules 401 and a similarly shaped loading track 410. Loading track410 includes cartridge carriers 411, similar to those described insystem 300, that transport cartridges to the loader for loading into thehexagonal array. FIG. 14C shows system 500, which includes a circulararray of modules 501 and a pair of linear loading tracks 510 thattransport cartridges directly to a pair of loaders on each side of thearray. Such linear tracks can include any features of the loading tracksdescribed herein or any suitable transport mechanism as would be knownto one of skill in the art. FIG. 14D shows system 600, which includestwo circular arrays of modules and a dumbbell shaped loading track 610that transports cartridges to either of the module arrays. As can beseen, loading track 610 can transport a cartridge to any of the loadersassociated with either of the module arrays. Such an approach allows thecartridges to be distributed between multiple arrays regardless ofwhether the cartridge is placed on the loading track 610. Alternatively,the cartridges could be allocated to a particular array, as desired. Inthis embodiment, loading track 610 utilizes carriers 611 such that thosedescribed above in system 300. It is appreciated that loading trackcould include any loading track feature described herein or could useany suitable alternate transport mechanism. While certain shapes of themodule arrays and loading tracks have been described, it is appreciatedthat various other shapes and arrangements could be utilized inaccordance with the principles described herein.

In the foregoing specification, the invention is described withreference to specific embodiments thereof, but those skilled in the artwill recognize that the invention is not limited thereto. Variousfeatures, embodiments and aspects of the above-described invention canbe used individually or jointly. Further, the invention can be utilizedin any number of environments and applications beyond those describedherein without departing from the broader spirit and scope of thespecification. The specification and drawings are, accordingly, to beregarded as illustrative rather than restrictive. It is recognized thatthe terms “comprising,” “including,” and “having,” as used herein, arespecifically intended to be read as open-ended terms of art.

1. A handling system for high throughput processing of a plurality ofbiological samples, each being within a respective diagnostic assaycartridge of a plurality of diagnostic assay cartridges, the systemcomprising: an array support assembly adapted to support a plurality ofdiagnostic assay modules in an array having at least two dimensions,each diagnostic assay module comprising a diagnostic assay systemadapted for receiving a diagnostic assay cartridge of the plurality andperforming a diagnostic assay on the biological sample within therespective cartridge; and a loader adapted to load the plurality ofdiagnostic assay cartridges within the plurality of diagnostic assaymodules while supported within the array support assembly, wherein thearray support assembly is movable relative the loader such that thediagnostic assay cartridge is loadable in any of the diagnostic assaymodules within the array by moving the array support structure relativethe loader in combination with the loader.
 2. The system of claim 1,wherein each of the diagnostic assay modules is adapted to perform adiagnostic assay independent from each other.
 3. The system of claim 1,wherein the array support assembly is configured so as to define acylindrical array.
 4. The system of claim 1, wherein the array comprisesa plurality of horizontal rows and the loader is translatable along asubstantially vertical axis so as to be movable between horizontal rowsof the cylindrical array.
 5. The system of claim 1, wherein the loaderincludes a grasper adapted to insert a cartridge supported by thegrasper along a horizontal axis from a grasped position within thegrasper to a loaded position within a diagnostic assay module of thearray.
 6. The system of claim 5, wherein the grasper is further adaptedto unload a cartridge loaded in a diagnostic assay module within thearray from the loaded position and transport the cartridge away from therespective module.
 7. The system of claim 5, wherein the grasper isfurther adapted to concurrently support at least two cartridges of theplurality of cartridges to facilitate any of: consecutive loading of theat least two cartridges, consecutive unloading of the at least twocartridges from respective loaded positions, unloading of one cartridgeof the at least two cartridges from a given module and subsequentloading of another cartridge of the at least two cartridges within thesame module, and unloading of one cartridge of the at least twocartridges from a given module and subsequent loading of anothercartridge of the at least two cartridges within a different module. 8.The system of claim 1, wherein the array support structure comprises astack of circular frames separated by slip rings that transmit power andcommunication data through a rotating union such that each module has adirect power and communication coupling.
 9. The system of claim 8,wherein each of the diagnostic assay modules comprises a rechargeablepower source that is wirelessly rechargeable by near-field energytransfer.
 10. The system of claim 1, wherein the array support assemblyincludes one or more sensors associated with each module within thearray, the one or more sensors being adapted to determine the locationof the modules within the array.
 11. The system of claim 7, furthercomprising: a controller having an input and an output, the controllerbeing configured to output a control command to the loader to load adiagnostic assay cartridge in a particular diagnostic assay module ofthe plurality in response to an input received from the one or moresensors that the diagnostic assay module is available for loading. 12.The system of claim 11, wherein the controller is configured todetermine a preferred diagnostic assay module from a plurality ofavailable diagnostic assay modules based on any of: proximity, atemperature measurement, a load balance, a heat balance, a distributionamong levels or within a respective level, a time length of assay, orany combination thereof.
 13. The system of claim 11, wherein the one ormore sensors are further configured to obtain a unique ID of each adiagnostic assay module and an associated cartridge loaded therein. 14.The system of claim 11, wherein each diagnostic assay module includes awireless communication unit adapted to communicate with the controller.15. The system of claim 12, wherein the wireless communication unit ofeach diagnostic assay module is configured to communicate to thecontroller that a diagnostic assay cartridge is associated with aparticular diagnostic assay module of the plurality after loading of thecartridge in the respective module.
 16. The system of claim 12, whereinthe controller is adapted to track which diagnostic assay module of theplurality is associated with each diagnostic assay cartridge of theplurality.
 17. The system of claim 12, wherein the controller is adaptedto output a command to the loader to load a diagnostic assay cartridgewithin a diagnostic assay module that is not already associated with adiagnostic assay cartridge.
 18. The system of claim 17, wherein thecontroller is further adapted to output to the loader a command tounload a particular diagnostic assay cartridge after receiving an inputthat a diagnostic result has been received from the diagnostic assaymodule associated with the respective cartridge.
 19. The system of claim1, wherein the system further includes a waste receptacle disposedbeneath the array support, wherein the loader is further adapted tounload spent diagnostic assay cartridges for collection and discardingwithin the waste receptacle.
 20. The system of claim 1, wherein thesystem further comprises: a loading track that conveys a plurality ofdiagnostic assay cartridges to the loader.
 21. The system of claim 20,wherein the loading track defines a plurality of recesses adapted toreceive the plurality of diagnostic assay cartridges.
 22. The system ofclaim 21 wherein each recess is configured to maintain each of theplurality of diagnostic assay cartridges in a particular position and/ororientation relative the loading track to facilitate loading with theloader when received.
 23. The system of claim 20, wherein the loaderincludes a grasper adapted to grasp a diagnostic assay cartridgeconveyed by the loading track when disposed at a particular loadingposition.
 24. The system of claim 20, wherein the array support definesa cylindrical array and the loading track is a ring that rotates aroundthe cylindrical array.
 25. The system of claim 24, wherein thering-shaped loading track and the cylindrical array rotate about acommon longitudinal axis and the ring-shaped loading track is adapted torotate independently from the cylindrical array.
 26. The system of claim20, wherein the loading track includes one or more sensors adapted todetect when one or more diagnostic assay cartridges are placed in theloading track.
 27. The system of claim 26, wherein the loading track isadapted to transport the one or more diagnostic assay cartridges towardthe loader in response to detection of the one or more cartridges. 28.The system of claim 1, further comprising: an air cooling system thatdirects air through a central column of the array assembly and througheach level of the array assembly so as to maintain the entire arrayassembly within a range of suitable temperatures.
 29. The system ofclaim 28, wherein the range of suitable temperatures is between 65 and95 degrees Fahrenheit to facilitate a PCR analysis.
 30. The system ofclaim 28, wherein the air cooling system includes a baffle between eachlevel of the array assembly such that air flow is, at least partly,separated between levels.
 31. The system of claim 28, wherein the aircooling system includes an external air cooler communicatively coupledwith one or more sensors in one or more levels of the array assembly.32. The system of claim 1, wherein each of the diagnostic assay modulesis fixedly secured within the array support assembly yet remainsremovable to allow repair and/or replacement.
 33. The system of claim 1,wherein the array support assembly defines a cylindrical array having adiameter of about 34″ or less and a height of 80″ or less when securedwithin the assembled system so as to facilitate transport of the systemthrough a standard-sized doorway.
 34. The system of claim 1, wherein thearray support assembly comprises a plurality of stacked circular framesdefining an open central column.
 35. The system of claim 31, wherein thesystem further includes an integrated cooling system that includes: oneor more cooling fans that draw a cool air intake upward from a bottom ofthe open central column toward a top of the open central column.
 36. Thesystem of claim 32, wherein the system further includes circular bafflesbetween each row so as to direct cooling air from the open centralcolumn directly to each row of modules within the cylindrical array. 37.The system of claim 1, wherein the array support assembly is acylindrical array that supports at least 50 modules and includes atleast two stacked rows.
 38. The system of claim 1, wherein the arraysupport assembly is a cylindrical array, each row supporting 25 modules,and having at least 4 rows such that the array support assembly supportsat least 100 modules.
 39. The system of claim 1, wherein the arraysupport assembly comprises two cylindrical arrays, each row supporting25 modules, and each cylindrical array having at least 4 rows such thatthe system supports 200 modules.
 40. The system of claim 20, furthercomprising: a cartridge preparer configured to perform one or moresample processes on a fluid sample within a diagnostic assay cartridgebefore analysis and to subsequently load the prepared diagnostic assaycartridge within the loading track.
 41. A method of handling a pluralityof biological samples with a high throughput processing system, each ofthe plurality of biological samples being within a diagnostic assaycartridge of a plurality of diagnostic assay cartridges, the methodcomprising: receiving the plurality of diagnostic assay cartridges in ahigh throughput processing system; and loading, with a loader, each ofthe plurality of diagnostic assay cartridges into a respectivediagnostic assay module of a plurality of diagnostic assay moduleswithin an array support defining an array having at least twodimensions, each diagnostic assay module comprising a diagnostic assaysystem adapted for receiving a diagnostic assay cartridge of theplurality and performing a diagnostic assay on a biological samplewithin the respective cartridge, wherein loading comprises moving thearray support relative the loader such that the diagnostic assaycartridge is loadable in any of the diagnostic assay modules within thearray by moving the array support structure relative the loader incombination with the loader. 42-70. (canceled)